132 J. Cosmet. Sci., 74, 132–142 (March/April 2023) Address all correspondence to Mariana Brito da Cruz, mariana.cruz@campus.ul.pt Hyaluronic Acid Aesthetic Fillers: A Review of Rheological and Physicochemical Properties PATRÍCIA PAULINO, MARIANA BRITO DA CRUZ AND VIRGÍNIA SANTOS Faculdade de Medicina Dentária da Universidade de Lisboa, Lisboa, Portugal (P.P., V.S.) Unidade de Investigação em Ciências Orais e Biomédicas (UICOB), Faculdade de Medicina Dentária da Universidade de Lisboa, Lisboa, Portugal (M.B.D.C.) Accepted for publication July 01, 2023. Synopsis Hyaluronic acid’s (HA) main functions are absorbing water into the tissues and structuring the skin. It is mostly used in dermal fillers, treatments for certain diseases, and wound healing. This study intends to review current literature of HA’s rheology and its physicochemical properties as an injectable filler. Data were acquired from articles concerning HA-based biomaterials published within the last 25 years in PubMed and ScienceDirect. The MeSH terms “hyaluronic acid” and “dermal fillers,” were used either alone or combined with “rheology,” “physicochemical concepts,” “cross-linking reagents,” “viscoelastic substances,” “cohesivity,” and “cosmetic techniques.” Some articles not found during the initial search were chosen from the reference lists of previously selected publications. All articles that fit in the theme were considered valid regardless of study type. Available literature describes intrinsic properties of HA as a glycosaminoglycan. As an injectable filler, its rheology (viscoelasticity and cohesivity) and its physicochemical properties (cross-linking, hydrophilia, particle size, and HA concentration) define its clinical behavior by influencing its longevity, lifting capacity, resistance to external forces, and needle extrusion force. HA is promising as a dermal filler and healing agent. Understanding its properties is essential, as each patient benefits from different products. Future research should continue to explore these properties. INTRODUCTION Hyaluronic acid or hyaluronan (HA) is the most abundant glycosaminoglycan present in the human dermis, with around 50% of total body HA being found in the skin, and a component of all mammalians’ connective tissue. HA constitutes a compound of cell surfaces and extracellular matrix in the skin, eyes, joints and muscles, and umbilical cord. Its main functions are to draw water into the tissues, volumizing and giving structure to the skin by binding collagen and elastin fibres into a supportive matrix.1-4 Additionally, HA intervenes in inflammation regulation, drug delivery, angiogenesis, cell migration and proliferation (caused by HA binding itself specifically to proteins that are responsible for these processes, whether they are in the extracellular matrix, on the cell surface, where they’re called hyaladherins, or in the cellular cytosol), wound healing (based on its